Matrix metalloproteinase (MMP)-2 gene polymorphisms affect circulating MMP-2 levels in patients with migraine with aura

Matrix metalloproteinases (MMP) are involved in the disruption of blood–brain barrier (BBB) during migraine attacks. In the present study, we hypothesized that two functional polymorphisms (C^− 1306T and C^− 735T) in MMP-2 gene and MMP-2 haplotypes are associated with migraine and modify MMP-2 and tissue inhibitor of MMP (TIMP)-2 levels in migraine. Genotypes for MMP-2 polymorphisms were determined by real time-PCR using Taqman allele discrimination assays. Haplotypes were inferred using the PHASE program. Plasma MMP-2 and TIMP-2 concentrations were measured by gelatin zymography and ELISA, respectively, in 148 healthy women without history of migraine and in 204 women with migraine (153 without aura; MWA, and 51 with aura; MA). Patients with MA had higher plasma MMP-2 concentrations and MMP-2/TIMP-2 ratios than patients with MWA and controls (P < 0.05). While MMP-2 genotype and haplotype distributions for the polymorphisms were similar among the groups (P > 0.05), we found that the CC genotype for C^− 735T polymorphism and the CC haplotype were associated with higher plasma MMP-2 concentrations in MA group (P < 0.05). Our findings may help to understand the role of MMP-2 and its genetic variants in the pathophysiology of migraine and to identify a particular group of migraine patients with increased MMP-2 levels that would benefit from the use of MMP inhibitors.     

SNV and haplotype analysis reveals new CSRP1 variants associated with growth and carcass traits

The cysteine and glycine-rich protein 1 and 2 genes (CSRP1 and CSRP2) are an effective growth factor in promoting skeletal muscle growth in vitro and vivo. However, in cattle, the information on the CSRP1 and CSRP2 genes is very limited. The aim of this study was to examine the association of the CSRP1 and CSRP2 variants with growth and carcass traits in cattle breeds. Three single nucleotide variants (SNVs) were identified within the bovine CSRP1 gene, whereas CSRP2 gene has not detected any SNVs, using DNA pooled sequencing, PCR-RFLP, and forced PCR-RFLP methods. These SNVs include g. 801T>C (Intron 2), g. 46T>C (Exon 3) and g. 99C>G (Intron 3). Besides, we also investigated haplotype frequencies and linkage disequilibrium (LD) coefficients for three SNVs in all study populations. LD and haplotype structure of CSRP1 were different between breeds. The result of haplotype analysis demonstrated eight haplotype present in QC (Qinchuan) and one haplotype in CH (Chinese Holstein). Only haplotype 1 (TTC), shared by all two populations, comprised 10.74% and 100.00%, of all haplotypes observed in QC and CH, respectively. Haplotype 5 (CTC) had the highest haplotype frequencies in QC (30.98%) and haplotype 1 had the highest haplotype frequencies in CH (100.00%). The statistical analyses indicated that one single SNV and 19 combined haplotypes were significantly or highly significantly associated with growth and carcass traits in the QC cattle population (P < 0.05 or P < 0.01). Quantitative real-time PCR (qRT-PCR) analyses showed that the bovine CSRP1 and CSRP2 genes were widely expressed in many tissues. The results of this study suggest that the CSRP1 gene possibly is a strong candidate gene that affects growth and carcass traits in the Chinese beef cattle breeding.     

The polymorphism in the promoter region of metallothionein 1 is associated with heat tolerance of scallop Argopecten irradians

Metallothioneins (MTs), a superfamily of cysteine-rich proteins, perform multiple functions, such as maintaining homeostasis of essential metals, detoxification of toxic metals and scavenging of oxyradicals. In this study, the promoter region of a metallothionein (MT) gene from Bay scallop Argopecten irradians (designed as AiMT1) was cloned by the technique of genomic DNA walking, and the polymorphisms in this region were screened to find their association with susceptibility or tolerance to high temperature stress. One insert–deletion (ins–del) polymorphism and sixteen single nucleotide polymorphisms (SNPs) were identified in the amplified promoter region. Two SNPs, − 375 T–C and − 337 A–C, were selected to analyze their distribution in the two Bay scallop populations collected from southern and northern China coast, which were identified as heat resistant and heat susceptible stocks, respectively. There were three genotypes, T/T, T/C and C/C, at locus − 375, and their frequencies were 25%, 61.1% and 13.9% in the heat susceptible stock, while 34.2%, 42.1% and 23.7% in the resistant stock, respectively. There was no significant difference in the frequency distribution of different genotypes between the two stocks (P > 0.05). In contrast, at locus − 337, three genotypes A/A, A/C and C/C were revealed with the frequencies of 11.6%, 34.9% and 53.5% in the heat susceptible stock, while 45.7%, 32.6% and 21.7% in the heat resistant stock, respectively. The frequency of C/C genotype in the heat susceptible stock was significantly higher (P < 0.01) than that in the heat resistant stock, while the frequency of A/A in the heat resistant stock was significantly higher (P < 0.01) than that in the heat susceptible stock. Furthermore, the expression of AiMT1 mRNA in scallops with C/C genotype was significantly higher than that with A/A genotype (P < 0.05) after an acute heat treatment at 28 °C for 120 min. These results implied that the polymorphism at locus − 337 of AiMT1 was associated with the susceptibility/tolerance of scallops to heat stress, and the − 337 A/A genotype could be a potential marker available in future selection of Bay scallop with heat tolerance.     

Methylenetetrahydrofolate reductase 677TT genotype might be associated with an increased lung cancer risk in Asians

Background

The association between methylenetetrahydrofolate reductase (MTHFR) 677C > T polymorphism and lung cancer risk has been studied in various populations with conflicting results. The aim of this study was to assess the association strength by a meta-analysis of published studies.

Methods

We searched PubMed and Chinese Biomedical (CBM) databases for relevant literatures published by July 18, 2012. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to assess the strength of the association.

Results

A total of 20 studies comprising 11,653 cases and 12,032 controls were included in the final meta-analysis. Using the random effect model, we found that MTHFR 677TT variant genotype was associated with an increased lung cancer risk (OR = 1.26, 95% CI = 1.05–1.50, P = 0.011 for TT vs. CC; OR = 1.19, 95% CI = 1.03–1.37, P < 0.001 for TT vs. CC + CT; OR = 1.11, 95% CI = 1.02–1.22, P = 0.017 for T allele vs. C allele). In the further stratified analyses, the increased lung cancer risk was found in Asian subjects (OR = 1.31, 95% CI = 1.01–1.71, P = 0.045 for TT vs. CC; OR = 1.17, 95% CI = 1.00–1.38, P = 0.048 for TT vs. CC + CT). There were no evidences for obvious publication bias in the overall meta-analysis and Asian subjects.

Conclusions

MTHFR 677TT genotype might increase the susceptibility of lung cancer, especially in Asians.